Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1MILTK)

• DOT Name: LYR motif-containing protein 9 (LYRM9)
• Gene Name: LYRM9
• Related Disease: Small-cell lung cancer
• UniProt ID: LYRM9_HUMAN
• Pfam ID: PF05347
• Sequence:
  MAPLPGAELVRRPLQLYRYLLRCCQQLPTKGIQQHYKHAVRQSFRVHSDEDNPERIQQII
  KRAIEDADWIMNKYKKQN

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Imatinib	DM7RJXL	Approved	LYR motif-containing protein 9 (LYRM9) affects the response to substance of Imatinib.	[13]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of LYR motif-containing protein 9 (LYRM9).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of LYR motif-containing protein 9 (LYRM9).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of LYR motif-containing protein 9 (LYRM9).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of LYR motif-containing protein 9 (LYRM9).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of LYR motif-containing protein 9 (LYRM9).	[6]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of LYR motif-containing protein 9 (LYRM9).	[7]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of LYR motif-containing protein 9 (LYRM9).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of LYR motif-containing protein 9 (LYRM9).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of LYR motif-containing protein 9 (LYRM9).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of LYR motif-containing protein 9 (LYRM9).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of LYR motif-containing protein 9 (LYRM9).	[10]

References

• [1] Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer.Nat Genet. 2012 Oct;44(10):1111-6. doi: 10.1038/ng.2405. Epub 2012 Sep 2.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [7] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [8] Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro. Oncotarget. 2014 Dec 30;5(24):12891-907.
• [9] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Identification of Genes That Modulate Susceptibility to Formaldehyde and Imatinib by Functional Genomic Screening in Human Haploid KBM7 Cells. Toxicol Sci. 2016 May;151(1):10-22. doi: 10.1093/toxsci/kfw032. Epub 2016 Mar 22.